INTRO Approximately 300 to 550 children per 100,000 sustain a mild traumatic brain injury (mTBI) each year, where about 25-30% have long-term cognitive problems. Following mTBI, free water (FW) accumulation occurs in white matter (WM) tracts. Diffusion tensor imaging (DTI) can be used to investigate structural integrity following mTBI. Compared to conventional DTI, NODDI orientation dispersion index (ODI) and fraction of isolated free water (FISO) metrics may allow a more advanced insight into microstructural damage following pediatric mTBI. METHODS In this longitudinal study we used NODDI to explore whole-brain and tract specific differences in ODI and FISO in children with persistent symptoms after mTBI (n=80) and children displaying clinical recovery (n=32) at 1- and 2-3 months post-mTBI compared to healthy controls (HCs; n=21). Two-way repeated measure ANOVA and voxel-wise two-sample t-tests were conducted to compare whole-brain and tract-specific diffusion across groups. All results were corrected at pFDR<0.05. We also examined the association between NODDI metrics and clinical outcomes, using logistic regression to investigate the value of NODDI metrics in predicting future recovery from mTBI. RESULTS Whole-brain ODI was significantly increased in symptomatic participants compared to HCs at both one and two-months post-injury, where the uncinate fasciculus (UF) and inferior fronto-occipital fasciculus (IFOF)) were particularly implicated. Using region of interest (ROI) analysis in significant WM, bilateral IFOF and UF voxels, symptomatic participants had the highest ODI in all ROIs. ODI was lower in asymptomatic participants, and healthy controls had the lowest ODI in all ROIs. No changes in FISO were found across groups or over time. White matter ODI was moderately correlated with a higher youth-reported post-concussion symptom inventory (PCSI) score. With 87% predictive power, ODI (1 month post-injury) and clinical predictors (age, sex, PCSI score, attention scores) were a more sensitive predictor of recovery at 2-3 months post-injury than FA and clinical predictors, or clinical predictors alone. FISO could not predict recovery at 2-3 months post-injury. DISCUSSION AND CONCLUSIONS ODI was significantly increased in symptomatic children following mTBI compared to healthy controls at 1- month post-injury, and progressively decreased over time alongside clinical recovery. We found no significant differences in FISO between groups or over time. White matter ODI at 1-month was a more sensitive predictor of clinical recovery at 2-3 months post-injury compared to FA, FISO or clinical measures alone. Our results show evidence of ongoing microstructural reorganisation or neuroinflammation between 1- and 2-3 months post-injury, further supporting delayed return to play in children who remain symptomatic. We recommend future research examining the clinical utility of NODDI following mTBI to predict recovery or persistence of post-concussion symptoms and thereby inform management of mTBI.

中文翻译：

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轻度创伤性脑损伤后症状持续存在的儿童正在进行的脑微结构重组的证据：NODDI DTI 分析。

简介 每年，每 100,000 名儿童中约有 300 至 550 名儿童遭受轻度创伤性脑损伤 (mTBI)，其中约 25-30% 存在长期认知问题。mTBI 后，白质 (WM) 束中发生游离水 (FW) 积累。弥散张量成像 (DTI) 可用于研究 mTBI 后的结构完整性。与传统的 DTI 相比，NODDI 取向色散指数 (ODI) 和分离自由水分数 (FISO) 指标可以更深入地了解儿科 mTBI 后的微观结构损伤。方法 在这项纵向研究中，我们使用 NODDI 探讨 mTBI 后持续症状的儿童 (n=80) 和 1-3 岁和 2-3 岁时表现出临床恢复的儿童 (n=32) 的 ODI 和 FISO 的全脑和束流特异性差异与健康对照（HC；n=21）相比，mTBI 后几个月。进行双向重复测量方差分析和体素双样本 t 检验，以比较各组的全脑和脑束特异性扩散。所有结果均在 pFDR<0.05 时进行校正。我们还检查了 NODDI 指标与临床结果之间的关联，使用逻辑回归来研究 NODDI 指标在预测 mTBI 未来恢复方面的价值。结果 在受伤后 1 个月和 2 个月，有症状参与者的全脑 ODI 显着增加，其中钩束 (UF) 和额枕下束 (IFOF) 尤其受影响。通过对显着 WM、双边 IFOF 和 UF 体素进行感兴趣区域 (ROI) 分析，有症状的参与者在所有 ROI 中具有最高的 ODI。无症状参与者的 ODI 较低，而健康对照者的 ODI 在所有 ROI 中最低。未发现 FISO 在各组之间或随着时间的推移发生变化。白质 ODI 与青少年报告的较高脑震荡后症状清单 (PCSI) 评分呈中度相关。ODI（受伤后 1 个月）和临床预测因素（年龄、性别、PCSI 评分、注意力评分）具有 87% 的预测能力，是比 FA 和临床预测因素更敏感的损伤后 2-3 个月恢复预测因素，或单独的临床预测因子。FISO 无法预测受伤后 2-3 个月的恢复情况。讨论和结论 受伤后 1 个月，与健康对照组相比，mTBI 后有症状的儿童的 ODI 显着增加，并随着临床恢复而随着时间的推移逐渐下降。我们发现不同组之间或不同时间段内的 FISO 没有显着差异。与单独的 FA、FISO 或临床测量相比，1 个月时的白质 ODI 是损伤后 2-3 个月临床恢复的更敏感的预测因子。我们的结果显示，有证据表明受伤后 1 个月至 2-3 个月内正在进行微观结构重组或神经炎症，这进一步支持仍有症状的儿童延迟返回玩耍。